Abstract: :
Purpose: It is widely accepted that glutamate (Glu)-mediatedexcitotoxic neuronal degeneration is involved in various retinaldisorders. However, under normal conditions the retina can beexposed to high concentrations of exogenous Glu without toxicconsequences. In a rat retinal preparation, Glu, at concentrationsup to 1 mM, induces Müller cell swelling but not excitotoxicneuronal damage. The reversibility of Müller cell swellingafter Glu washout indicates that Müller cell swelling isnot a toxic consequence. It is presently unclear whether Gludirectly induces Müller cell swelling. It is possible thatglutamine (Gln), a metabolite of Glu, induces Müller cellswelling by acting as an osmolyte. To examine this possibility,we used methionine sulfoximine (MSO), an inhibitor of glutaminesynthetase, the enzyme that catalyzes the synthesis of Gln fromGlu and ammonia.Methods: Ex vivo rat retinas were exposed to1mM Glu or 1mM Gln. Glu was combined with 1 mM ammonia or withMSO. Results were analyzed histologically.Results:Glu-mediatedMüller cell swelling was masked by co-administration ofammonia. The reversibility of Müller cell swelling wasblocked by MSO following 20 min administration of Glu. Gln alonefailed to induce Müller cell swelling.Conclusion: Glu-mediatedMüller cell swelling is unlikely to result from accumulationof Gln. Rather, metabolism to Gln is crucial for reversibilityof Glu-mediated Müller cell swelling. Although ammoniacan be toxic to the CNS, ammonia is necessary for Glu metabolism.These observations suggest that the metabolism of Glu to Glnis important for controlling Glu-mediated toxicity in the retina.